|Department Affiliations||Willard and Lillian Hackerman Professor in Radiation Oncology Director, Division of Molecular Radiation Sciences|
|Office Phone||(410) 502-9748|
|SOM Address||Room 444 Cancer Research Building II|
Our research focuses on the relevance and implications of cellular DNA damage responses in cancer. A particular aspect in this context is the function and regulation of p53 tumor suppressor, and attempts to revoke its activity in specific types of cancer. We have identified novel p53 activating small-molecule compounds, which are being tested for their efficacy in p53 pathway activation in various tumor cell models in vitro and in animal studies in vivo. We have presented findings of altered p53 and DNA damage checkpoint responses in prostate epithelial cells and tissue, which may indicate that a relaxed damage control could predispose to the highly frequent tumorigenic processes observed clinically. The studies aim at a transfer of findings arising from focused mechanistic studies into translational cancer research.
- Kurki, S., Latonen, L., and Laiho, M. Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization. J. Cell. Sci. 116: 3917-3925, 2003.
- Kurki, S., Peltonen, K., Latonen, L., Kiviharju, T., Ojala, P.M., Meek, D. and Laiho, M. Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation. Cancer Cell 5: 465-475, 2004.
- Sarek, G., Kurki, S., Enbäck, J., Iotzova, G., Haas, J., Laakkonen, P., Laiho, M., and Ojala, P.M. Therapeutic potential of small-molecule inhibitor of the p53-Mdm2 interaction in primary effusion lymphomas. J. Clin. Invest. 117: 1019-1028, 2007.
- Kiviharju, T., Jäämaa, S., Mönkkönen, M., Peltonen, K., Andersson, L.C., Medema, R., Peehl, D., and Laiho, M. Human prostate epithelium lacks DNA damage-induced checkpoint enforcement by inhibitory Cdk tyrosine 15 phosphorylation. Proc. Natl. Acad. Sci. USA 104: 7211-7216, 2007.